Post-Traumatic Stress Disorder (PTSD) affects 7-8% of the general population of the United States and approximately 15% of veterans returning from combat. The symptoms can persist for months or decades. Unfortunately, PTSD is often misdiagnosed and left untreated in affected civilian and military individuals, disrupting the quality of their lives, their families and children, as well as our healthcare system.
PTSD is a severely disabling anxiety disorder which can occur after mild traumatic brain injury (TBI), a subject has seen or experienced a traumatic event that involved the threat of injury or death and which can be found clinically in acute or chronic forms. Relevant traumatic experiences include experiencing or witnessing childhood abuse, vehicle accidents, medical complications, physical assaults, natural disasters, jail, or war. The symptoms of PTSD include, but are not limited to, intrusion of recurrent nightmares or daytime flashbacks, characterized by high anxiety, hyperarousal, which is a constant jumpy preparation for fight or flight and avoidance of contact with anything or anyone that might remind the patient of the trauma. Acute PTSD may resolve within 3-6 months, whereas chronic PTSD is a waxing and waning disorder that can persist for months, years, or decades. PTSD is often co-morbid with other psychiatric disorders, such as, but not limited to, depression, substance abuse, and suicidal thoughts.
Current diagnosis of PTSD is established on the basis of clinical history and subjective mental status examination, using a clinically structured interview, symptom checklists, or patient self-reports. These subjective tests, however, make it difficult to distinguish PTSD from other psychiatric disorders, resulting in difficult treatment decisions as to both treatment interventions and a more definitive understanding of the etiology. The existing limitations of current clinical assessment would benefit substantially from a more objective means to enhance the ability to identify PTSD in a patient and thus enabling the ability to differentiate PTSD from other psychiatric disorders in patients.
Treatments for PTSD include but are not limited to psychotherapy, such as but not limited to Cognitive Behavioral Therapy, pharmacotherapy, such as but not limited to serotonin-specific reuptake inhibitor (SSRI's). Many different pharmacological approaches have been investigated. For example, it is believed that Major Depressive Disorder (MDD) and PTSD have much in common, thus antidepressants, such as but not limited to the SSRI drugs fluoxitine (Prozac) and paroxatine (Paxil) are widely considered effective at treating some symptoms of PTSD. Other commonly administered SSRI antidepressants have included venlafaxine (Effexor) and sertraline (Zoloft).
Other commonly administered antipsychotics used to treat PTSD include but are not limited to mirtazapine (Remeron), olanzapine (Zyprexa) and quetiapione (Seroquel). The beta blocker propranolol has also been used to try to block memory formation in PTSD patients. Prazosin, an α1-selective adrenoceptor antagonist, has been reported to reduce trauma-related nightmares and sleep disturbances associated with PTSD.
Because PTSD can only be diagnosed through a personal interview of a patient, where the patient may be cognizant to give answers they know to be correct, the current methods leave it difficult to diagnose subjects suffering from these disorders. As a result, a majority of PTSD cases are often missed, misdiagnosed or left untreated in thousands of affected individuals. To date there are no clinical methods for diagnosing PTSD because of the lack of reliability, specificity and cost efficacy.
Biomarkers are increasingly used to diagnose diseases promptly and accurately, and to identify individuals at high risk for certain conditions and tendencies even before clinical manifestations arise. There are presently no biomarkers to validate the diagnosis or to serve as objective surrogate endpoints for therapy for PTSD.
Micro RNAs (μRNAs) are small (˜22 nucleotides) non-coding RNAs that can be posttranscriptional gene regulators for diverse biological processes. In circulation, μRNAs are considered as good biomarkers because they are highly stable in serum. Currently, however, there are no reports on the use of circulatory μRNAs as non-invasive biomarkers for the diagnosis of PTSD.
Despite today's technology with biomarker analysis, there remains an unmet need for prognostic indicators that can aid in the objective detection PTSD. In addition, there exists a need for a method of diagnosing PTSD, a need to monitor PTSD progression, a need for detecting PTSD prior to the onset of detectable symptoms and a need for clinical intervention with therapeutics. Finally, there remains for an unmet need for an in vitro diagnostic device to identify neurochemical markers to detect and/or diagnose PTSD.